Functional switching of GABAergic synapses by ryanodine receptor activation

Functional switching of GABAergic synapses by ryanodine receptor activation

Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892

Communicated by Bernhard Witkop, National Institutes of Health, Bethesda, MD (received for review May 26, 2000)

Abstract

The role of the ryanodine receptor (RyR) in modifiability of synapses made by the basket interneurons onto the hippocampal CA1 pyramidal cells was examined in rats. Associating single-cell RyR activation with postsynaptic depolarization increased intracellular free Ca²⁺ concentrations and reversed the basket interneuron–CA1 inhibitory postsynaptic potential into an excitatory postsynaptic potential. This synaptic transformation was accompanied by a shift of the reversal potential from that of chloride toward that of bicarbonate. This inhibitory postsynaptic potential–excitatory postsynaptic potential transformation was prevented by blocking RyR or carbonic anhydrase. Associated postsynaptic depolarization and RyR activation, therefore, changes GABAergic synapses from excitation filters to amplifier and, thereby, shapes information flow through the hippocampal network.

Footnotes

↵ * To whom reprint requests should be addressed at: Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke/National Institutes of Health, Building 36, Room 4A24, 36 Convent Drive, Bethesda, MD 20892. E-mail: mksun{at}codon.nih.gov.
Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.210396697.
Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.210396697
Abbreviations:

BAS,

basket interneurons;

BIC,

bicuculline;

cADP-ribose,

cyclic ADP-ribose;

[Ca2+]i,

intracellular free Ca2+ concentration;

EPSP,

excitatory postsynaptic potential;

GABA,

γ-aminobutyric acid;

IPSC,

inhibitory postsynaptic current;

IPSP,

inhibitory postsynaptic potential;

NEMM,

N-ethylmaleimide;

RR,

ruthenium red;

RyR,

ryanodine receptor;

SCH,

Schaffer collateral pathway